Boronic compounds

ABSTRACT

A process for the preparation of a diboronic acid ester comprising contacting diboronic acid with a suitable monoalcohol, diol or polyol, for a time and under conditions such that the diboronic acid reacts with the monoalcohol, diol or polyol to form the diboronic acid ester.

This application is a divisional application of U.S. application Ser.No. 09/581,216, filed Dec. 6, 2000, now U.S. Pat No. 6,346,639 (of whichthe entire disclosure of the pending, prior application is herebyincorporated by reference), which is a 371 of PCT/AU98/01072, filed Dec.23, 1998, and which was published in English.

The invention relates to boronic compounds, in particular to noveldiboron derivatives and organic boronic acid derivatives preparedtherefrom. The invention also relates to processes for the preparationof these derivatives. These diboron derivatives and organic boronic acidderivatives are useful intermediates in processes for covalently linkingorganic compounds.

Processes for forming covalent bonds between organic compounds, bothinter- and intra-molecular, are of particular importance to thesynthetic organic chemist. Many such reactions are known, each requiringits own special reaction conditions, solvents, catalysts, ringactivating groups etc. Some known types of coupling reactions includethe Grignard reaction, Heck reactions and Suzuki reactions (N. Migauraand A. Suzuki, Chem. Rev. 1995, 95, 2457-2483).

Substituted bi- and tri-aryl compounds are of great interest to thepharmaceutical and agrochemical industries. A great number of thesecompounds have been found to possess pharmaceutical activity, whileothers have been found to be useful herbicides. There is also interestfrom the polymer industry in polymers prepared by the linking togetherof organic compounds.

Conventional methods for covalently linking aromatic rings, such as byreaction of an appropriate Grignard reagent, involve harsh conditionsand are not suitable for aromatic rings with active hydrogen containingsubstituents. Substituents with active hydrogen atoms also can becomeinvolved in unwanted side reactions leading to undesirable products.Such substituents need to be protected prior to reaction. Boronic acidderivatives required for the Suzuki reaction are traditionallysynthesized through highly reactive organo metallic intermediates.

In view of the severity of the reaction conditions the range ofsubstituents which could be present during the linking reaction wasconsiderably limited, and the range of useful reaction media (solvents)was restricted to those which can be expensive, difficult to removeand/or toxic.

A difficulty associated with the known coupling reactions is the limitedcontrol of the functionality of the products, leading to complexmixtures which can be difficult to separate.

Some known diboron derivatives are relatively unstable compounds, whichdecompose readily in aqueous solution or on exposure to air. For thisreason, and a perceived difficulty in making the compounds, their use inchemical reaction is relatively unexplored.

It has now been found that diboron derivatives can be quite stable anduseful in the preparation of organic boronic acid derivatives, and thatproperties of the diboron derivatives can be adjusted to suit particularreaction conditions or to provide particular products by selection ofappropriate substituents.

Accordingly in a first aspect of the present invention there is provideda diboron derivative of formula (I)

where

R¹, R¹, R³ and R⁴ are each independently selected from the groupconsisting of optionally substituted allyl, optionally substitutedalkenyl, optionally substituted aryl, optionally substituted cycloalkyl,optionally substituted cycloalkenyl, and a group of the formula—(R⁵Q)_(m) R⁶ where Q is selected from O, S, NR⁷, optionally substitutedarylene and optionally substituted cycloalkylene, m is an integer from 1to 3, the or each R⁵ is independently an optionally substituted C₁-C₃alkylene, R⁶ is C₁-C₃ alkyl or hydrogen and

R⁷ is hydrogen or C₁-C₁₂ alkyl; and

each X is independently selected from O, S(O)_(n) and NR⁷, where n is aninteger of 0 to 3 and R⁷ is hydrogen or C₁-C₁₂ alkyl, or one or more of—NR¹R⁷, —NR²R⁷, —NR³R⁷ and —NR⁴R⁷ represent an optionally substituted 5or 6 membered heterocyclyl group,

provided that when each X is O and R¹ to R⁴ are identical, R¹ to R⁴ arenot unsubstituted straight chain akyl, phenyl or naphthyl, isopropyl, orphenyl substituted with alkyl; when each X is N(C₁-C₆ alkyl), R¹ to R⁴are not C_(1-C) ₆ alkyl and —NR¹R⁷, —NR²R⁷, —NR³R⁷ and —NR⁴R⁷ are notunsubstituted piperidyl or unsubstituted pyrolidinyl; when each X is NH,R¹ to R⁴ are not C₁-C₆ alkyl or unsubstituted phenyl; and when —XR¹ is—OCH₃, —XR² is —N(CH₃)₂ and —XR⁴ is —N(CH₃)₂, —XR³ is not OCH₃.

In a second aspect of the invention there is provided a diboronderivative of formula (II)

where X is independently selected from O, S(O)_(n) and NR⁷ where n is aninteger from 0 to 2, R⁷ is hydrogen or C₁-C₁₂ alkyl, and A¹ and A² aredivalent groups which may be the same or different, provided that wheneach X is O, A¹ and A² are not unsubstituted C₁-C₃ alkylene,1,1,2,2-tetramethylethylene, 2,2-dimethylpropylene,1,2-dialkoxycarbonylethylene, 1,2 diphenylethylene, 1 phenylethylene,unsubstituted phenylene or phenylene mono- or di-substituted with C₁-C₄alkyl; and when each X is S or NMe, both of A¹ and A² are not ethylene.

Preferably A¹ and A² are independently selected from optionallysubstituted alkylene, optionally substituted alkenylene, optionallysubstituted alkynylene, optionally substituted arylene, optionallysubstituted alkylarylene, optionally substituted cycloalkylene,optionally substituted cycloalkenylene, or a group of the formula—(R⁵Q)_(m)R⁶ where Q is selected from O, S, NR⁷, optionally substitutedarylene and optionally substituted cycloalkylene, m is an integer of 1to 3, R⁵ and R⁶ are independently an optionally substituted C₁-C₃alkylene, and R⁷ is hydrogen or C₁-C₁₂ alkyl. The divalent groups, A¹and A², may include a fused 5 or 6 membered aliphatic or aromatic ring.

In a third aspect of the present invention there is provided a diboronderivative of formula

where

R¹ and R² are each independently selected from the group consisting ofoptionally substituted alkyl, optionally substituted alkenyl, optionallysubstituted alkynyl, optionally substituted aryl, optionally substitutedcycloalkyl, optionally substituted cycloalkenyl, a group of the formula—(R⁵Q)_(m)R⁶ where Q is selected from O, S, NR⁷, optionally substitutedarylene and optionally substituted cycloalkylene, m is an integer of 1to 3, the or each R⁵ is independently an optionally substituted C₁-C₃alkylene, R⁶ is hydrogen or C₁-C₃ alky, and R⁷ is hydrogen or C₁-C₁₂alkyl;

each X is independently selected from O, S(O)_(n) and NR⁷, where n is aninteger of 0 to 3 and R⁷ is hydrogen or C₁-C₁₂ alky, or one or both of—NR¹R⁷ and —NR²R⁷ represent an optionally substituted 5 or 6 memberedheterocyclyl group; and

A is a divalent group;

provided that when R¹ and R² are Me and each X is NMe then A is notunsubstituted ethylene.

Preferably A is independently selected from optionally substitutedalkylene, optionally substituted alkenylene, optionally substitutedarylene, optionally substituted cycloalkylene, optionally substitutedcycloalkenylene, or a group of the formula —(R⁵Q)_(m)R⁶— where Q isselected from O, S, NR⁷, optionally substituted arylene and optionallysubstituted cycloalkylene, m is an integer of 1 to 3, R⁵ and R⁶ areindependently an optionally substituted C₁-C₃ alkylene, and R⁷ ishydrogen or C₁-C₁₂ alkyl. The divalent group A, may include a fusedaliphatic or aromatic ring or ring system.

The invention also provides a diboron derivative of formula (I)

or a diboron derivative of formula (II)

or a diboron derivative of formula (III)

where

R¹, R², R³ and R⁴ are each independently selected from the groupconsisting of optionally substituted alkyl, optionally substitutedalkenyl, optionally substituted aryl, optionally substituted cycloalkyl,optionally substituted cycloalkenyl, a group of the formula —(R⁵Q)_(m)R⁶where Q is selected from O, S, NR⁷, optionally substituted arylene andoptionally substituted cycloalkylene, m is an integer of 1 to 3, the orand each R⁵ is independently an optionally substituted C₁-C₃ alkylene,R⁶ is C₁-C₃ alkyl or hydrogen, and R⁷ is hydrogen or C₁-C₁₂ alkyl;

each X is independently selected from O, S(O)_(n) and NR⁷, where n is aninteger from 0 to 3, R⁷ is hydrogen or C₁-C₁, alkyl, or one or more of—NR¹R⁷, —NR²R⁷, —NR³R⁷ and —NR⁴R⁷ represent an optionally substituted 5or 6 membered heterocyclyl group,

and A, A¹ and A² are divalent groups which may or may not be different,wherein said derivative has one or more chiral centres and there is anenantiomeric excess of one form.

Preferably the enantiomeric excess is greater than 80%, and morepreferably greater than 90%.

In the above definitions, the term “alkyl”, used either alone or incompound words such as “alkenyloxyalkyl”, “alkylthio”, “alkylarnino” and“dialkylamino” denotes straight chain or branched alkyl, preferablyC₁₋₂₀ alkyl. Examples of straight chain and branched alkyl includemethyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl,tert-butyl, amyl, isoamyl, sec-amyl, 1,2-dimethylpropyl,1,1-dimethyl-propyl, hexyl, 4-methylpentyl, 1-methylpentyl,2-methylpentyl, 3-methylpentyl, 1,1-dimethylbutyl, 2,2-dimethylbutyl,3,3-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl,1,2,2,-trimethylpropyl, 1,1,2-trimethylpropyl, heptyl, 5-methoxyhexyl,1-methylhexyl, 2,2-dimethylpentyl, 3,3-dimethylpentyl,4,4-dimethylpentyl, 1,2-dimethylpentyl, 1,3-dimethylpentyl,1,4-dimethyl-pentyl, 1,2,3,-trimethylbutyl, 1,1,2-trimethylbutyl,1,1,3-trimethylbutyl, octyl, 6-methylheptyl, 1-methylheptyl,1,1,3,3-tetramethylbutyl, nonyl, 1-, 2-, 3-, 4-, 5-, 16 or7-methyl-octyl, 1-, 2-, 3-, 4- or 5-ethylheptyl, 1-, 2- or3-propylhexyl, decyl, 1-, 2-, 3-, 4-, 5-, 6-, 7- and 8-methylnonyl, 1-,2-, 3-, 4-, 5- or 6-ethyloctyl, 1-, 2-, 3- or 4-propylheptyl, undecyl,1-, 2-, 3-, 4-, 5-, 6-, 7-, 8- or 9-methyldecyl, 1-, 2- 3-, 4-, 5-, 6-or 7-ethylnonyl, 1-, 2-, 3-, 4- or 5-propyloctyl, 1-, 2- or3-butylheptyl, 1-pentylhexyl, dodecyl, 1-, 2-, 3-, 4-, 5-, 6-, 7-, 8-,9- or 10-methylundecyl, 1-, 2-, 3-, 4-, 5-, 6-, 7- or 8-ethyldecyl, 1-,2-, 3-, 4-, 5- or 6-propylnonyl, 1-, 2-, 3- or 4-butyloctyl1-2-pentylheptyl and the like.

The term “alkylene” denotes a divalent alkyl group as defined above.

The term “cycloalkyl” denotes cyclic alkyl groups, preferably C₃₋₂₀cycloalkyl. Examples of cycloalkyl include mono- or polycyclic alkylgroups such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl and the like.

The term “cycloalkylene” denotes a divalent cycloalkyl group as definedabove.

The term “alkenyl” denotes groups formed from straight chain or branchedalkenes including ethylenically mono-, di- or poly-unsaturated alkyl orgroups as previously defined, preferably C₂₋₂₀ alkenyl. Examples ofalkenyl include vinyl, allyl, 1-methylvinyl, butenyl, iso-butenyl,3-methyl-2-butenyl, 1-pentenyl, 1-hexenyl, 3-hexenyl, 1-heptenyl,3-heptenyl, 1-octenyl, 1-nonenyl, 2-nonenyl, 3-nonenyl, 1-decenyl,3-decenyl, 1,3-butadienyl, 1-4,pentadienyl, 1,3-hexadienyl,1,4-hexadienyl.

The term “alkenylene” denotes a divalent alkenyl group as defined above.

The term “cycloalkenyl” denotes cyclic alkene groups, preferably C₅₋₂₀cycloalkenyl. Examples of cycloalkenyl include (cyclopentenyl, methylcyclopentenyl, cyclohexenyl, cyclooctenyl, 1,3-cyclopentadienyl,1,3-cyclohexadienyl, 1,4-cyclohexadienyl, 1,3-cycloheptadienyl,1,3,5-cycloheptatrienyl and 1,3,5,7-cyclooctatetraenyl.

The term “cycloalkenylene” denotes a divalent cycloalkenyl group asdefined above.

The term “aryl” is used herein in the broadest sense to refer to anyaromatic ring or ring system, preferably having 3 to 20 carbon atoms.The ring or ring system may contain one or more heteroatoms selectedfrom N, S, and O. The aromatic rings may be carbocyclic, heterocyclic orpseudo aromatic, and may be mono or polycyclic ring systems. Examples ofsuitable rings include but are not limited to benzene, biphenyl,terphenyl, quaterphenyl, naphthalene, tetrahydronaphthalene,1-benzylnaphthalene, anthracene, dihydroanthracene, benzanthracene,dibenzanthracene, phenanthracene, perylene, pyridine, 4-phenylpyridine,3-phenylpyridine, thiophene, benzothiophene, naphthothiophene,thianthrene, furan, pyrene, isobenzofuramn, chromene, xanthene,phenoxathiin, pyrrole, imidazole, pyrazole, pyrazine, pyrimidine,pyridazine, indole, indolizine, isoindole, purine, quinoline,isoquinoline, phthalazine, quinoxaline, quinazoline, pteridine,carbazole, carboline, phenanthridine, acridine, phenanthroline,phenazine, isothiazole, isooxazole, phenoxazine and the like, each ofwhich may be optionally substituted. The term “pseudoaromatic” refers toa ring system which is not strictly aromatic, but which is stablized bymeans of delocalization of π electrons and behaves in a similar mannerto aromatic rings. Examples of pseudoaromatic rings include but are notlimited to furan, thiophene, pyrrole and the like.

The term “aliphatic ring or ring system” as used herein refers to anon-aromatic carbocyclic or heterocyclic ring or ring system, preferablyhaving from 3 to 20 carbon atoms. The ring or ring system may have oneor more double or triple bonds. Examples of suitable aliphatic ringsinclude but are not limited to cyclobutane, cyclopentadiene,cyclohexanone, cyclohexene, spiro-[4,5-decane] and hydrogenated orpartially hydrogenated aromatic rings as described above.

The term “arylene” as used herein denotes a divalent “aryl” moiety asdefined above.

As used herein, an “olefinic” compound refers to any organic compoundhaving at least one carbon to carbon double bond which is not part of anaromatic or pseudo aromatic system. The olefinic compounds may beselected from optionally substituted straight chain, branched or cyclicalkenes; and molecules, monomers and macromolecules such as polymers anddendrimers, which include at least one carbon to carbon double bond.Examples of suitable olefinic compounds include but are not limited toethylene, propylene, but-1-ene, but-2-ene, pent-1-ene, pent-2-ene,cyclopentene, 1-methylpent-2-ene, hex-1-ene, hex-2-ene, hex-3-ene,cyclohexene, hept-1-ene, hept-2-ene, hept-3-ene, oct-1-ene, oct-2-ene,cyclooctene, non-1-ene, non-4-ene, dec-1-ene, dec-3-ene, buta-1,3-diene,penta-1,4-diene, cyclopenta-1,4-diene, hex-1,4,diene,cyclohexa-1,3-diene, cyclohexa-1,4-diene, cyclohepta-1,3-diene,cyclohepta-1,3,5-triene and cycloocta-1,3,5,7-tetraene, each of whichmay be optionally substituted. Preferably the straight chain branched orcyclic alkene contains between 2 and 20 carbon atoms.

In this specification “optionally substituted” means that a group may ormay not be further substituted with one or more groups selected fromalkyl, alkenyl, alkynyl, aryl, halo, haloalkyl, haloalkenyl,haloalkynyl, haloaryl, hydroxy, alkoxy, alkenyloxy, aryloxy,aryloxyalkyl, benzyloxy, haloalkoxy, haloalkenyloxy, haloaryloxy,isocyano, cyano, formyl, carboxyl, nitro, nitroalkyl, nitroalkenyl,nitroalkynyl, nitroaryl, nitroheterocyclyl, amino, alkylamino,dialkylamino, alkenylamino, alkynylamino, arylamino, diarylamino,benzylamino, imino, alkylimino, alkenylimino, alkynylimino, arylimino,benzylimino, dibenzylamino, acyl, alkenylacyl, alkynylacyl, arylacyl,acylamino, diacylamino, acyloxy, alkylsulphonyloxy, arylsulphenyloxy,heterocyclyl, heterocycloxy, heterocyclamino, haloheterocyclyl,alkylsulphenyl, arylsulphenyl, carboalkoxy, carboaryloxy mercapto,alkylthio, benzylthio, acylthio, sulphonamido, sulfanyl, sulfo andphosphorus-containing groups.

The term “fused aliphatic or aromatic ring” as used herein in relationto divalent groups A, A and A² means that one or more of the bondsconnecting the X moieties of the compounds of formulae I, II or III ispart of an aliphatic or aromatic ring system.

As used herein the term “divalent group” refers to any group having twovalencies available for bonding with another chemical moiety. Examplesof suitable divalent groups include alkylene, alkenylene, cycloalkyleneand the like.

The term “acyl” as used herein refers to carbamoyl, aliphatic acyl groupand acyl group is referred to as heterocyclic acyl, preferably C₁₋₂₀acyl. Examples of acyl include carbamoyl; straight chain or branchedalkanoyl such as formyl, acetyl, propanoyl, butanoyl, 2-methylpropanoyl,pentanoyl, 2,2-dimethylpropanoyl, hexanoyl, heptanoyl, octanoyl,nonanoyl, decanoyl, undecanoyl, dodecanoyl, tridecanoyl, tetradecanoyl,pentadecanoyl, hexadecanoyl, heptadecanoyl, octadecanoyl, nonadecanoyland icosanoyl; alkoxycarbonyl such as methoxycarbonyl, ethoxycarbonyl,t-butoxycarbonyl, t-pentyloxycarbonyl and heptyloxycarbonyl;cycloalkylcarbonyl such as cyclopropylcarbonyl, cyclobutylcarbonyl,cyclopentylcarbonyl and cyclohexylcarbonyl; alkylsulfonyl such asmethylsulfonyl and ethylsulfonyl; alkoxysulfonyl such as methoxysulfonyland ethoxysulfonyl; aroyl such as benzoyl, toluoyl and naphthoyl;aralkanoyl such as phenylalkanoyl (e.g. phenylacetyl, phenylpropanoyl,phenylbutanoyl, phenylisobutylyl, phenylpentanoyl and phenylhexanoyl)and naphthylalkanoyl (e.g. naphthylacetyl, naphthylpropanoyl andnaphthylbutanoyl]; aralkenoyl such as phenylalkenoyl (e.g.phenylpropenoyl, phenylbutenoyl, phenylmethacryloyl, phenylpentenoyl andphenylhexenoyl and naphthylalkenoyl (e.g. naphthylpropenoyl,naphthylbutenoyl and naphthylpentenoyl); aralkoxycarbonyl such asphenylalkoxycarbonyl (e.g. benzyloxycarbonyl); aryloxycarbonyl such asphenoxycarbonyl and napthyloxycarbonyl; aryloxyalkanoyl such asphenoxyacetyl and phenoxypropionyl; alkylcarbamoyl such asphenylcarbamoyl; arylthiocarbamoyl such as phenylthiocarbamoyl;arylglyoxyloyl such as phenylglyoxyloyl and naphthylglyoxyloyl;arylsulfonyl such as phenylsulfonyl and napthylsulfonyl;heterocycliccarbonyl; heterocyclicalkanoyl such as thienylacetyl,thienylpropanoyl, thienylbutanoyl, thienylpentanoyl, thienylhexanoyl,thiazolylacetyl, thiadiazolylacetyl and tetrazolylacetyl;heterocyclicalkenoyl such as heterocyclicpropenoyl,heterocyclicbutenoyl, heterocyclicpentenoyl and heterocyclichexenoyl;and heterocyclicglyoxyloyl such as thiazolylglyoxyloyl andthienylglyoxyloyl.

The diboron derivatives may be made following the method of Brothertonet al. [R. J. Brotherton, A. L. McCloskey, L. L. Peterson and H.Steinberg, J. Amer. Chem. Soc. 82, 6242 (1960); R. J. Brotherton, A. L.McCloskey, J. L. Boone and H. M. Manasevit, J. Amer. Chem. Soc. 82, 6245(1960)]. In this process B(NMe₂)₃, obtained by reaction of BCl₃ withNHMe₂, is converted to BrB(NMe₂)₂ by reaction with a stoichiometricamount of BBr₃. Reduction in refluxing toluene with sodium metal givesthe diboron compound [B(NMe₂)₂]₂ which, after purification bydistillation, can be reacted with the alcohol (for example, pinacol orneopentanediol) in the presence of a stoichiometric amount (fourequivalents) of HCl to give the desired ester product.

With many alcohols this reaction is unsatisfactory, the reaction beingslow and complete removal of the amine being difficult unless anhydrousmineral acid (four equivalents) are added to the reaction.

An aspect of the present invention is the discovery that esters oftetrahydroxydiboron can be readily synthesised in near quantitativeyield by the reaction of diboronic acid (tetrahydroxydiboron) withalcohols (including diols and polyols) and this reaction does notrequire the presence of acids. Furthermore, it has been found that thereaction of tetrahydroxydiboron with certain diols can be carried outwith advantage in the presence of simple monoalcohols such as methanolor ethanol without these monoalcohols being incorporated in the finalreaction products. These reactions, in the presence of monoalcohols,show that tetrahydroxydiboron esters of these monoalcohols readilyundergo transesterification with diols that can form ring structures ona boron atom. The transesterification represents a further procedure forthe production of esters of tetrahydroxydiboron. These reactions can beperformed in a variety of solvents or mixtures thereof.

Accordingly in a further aspect of the present invention there isprovided a process for the preparation of a diboronic acid estercomprising contacting diboronic acid with a suitable monoalcohol, diolor polyol for a time and under conditions such that the diboronic acidreacts with the diol or polyol to produce the diboron derivative.

Unlike the literature procedure, the process according to this aspect ofthe present invention lends itself readily to the synthesis oftetrahydroxydiboron esters with acid sensitive alcohols. The synthesisof tetrahydroxydiboron esters with alcohols possessing basicfunctionalities are difficult using the known literature method sincethe products obtained are partially or fully protonated on their basicfunctionalities. The process according to this aspect of the presentinvention does not have this inherent problem.

In the prior art procedure the side product, the acid salt of the amine,must be removed to obtain pure product. A major advantage of the presentprocess is that product obtained is sufficiently pure that it cangenerally be used without the need for further purification.

The diboron derivatives according to the present invention are useful inthe preparation of organic boronic acid derivatives, and by selection ofappropriate substituents and reactants, it is possible to use thediboron derivatives to form organic boronic acid derivatives which areuseful in organic coupling reactions.

The organic boronic acid derivatives are generally prepared by reactionof a diboron derivative of this invention and an organic compound in thepresence of a Group VIII metal catalyst. In order to participate in sucha reaction the organic compound should possess a boron reactive site.

The boron reactive site may be a halogen or halogen-like substituent onthe organic compound, a carbon to carbon double or triple bond, orleaving group located in an allylic position.

In the case of halogen or halogen-like substituents, and allylic leavinggroups, the diboron derivative displaces the group in a substitutionreaction to form an organic boronic acid derivative. In the case ofreaction with double and triple carbon-to-carbon bonds in the presenceof platinum and like catalysts, the diboron compound tends to undergo anaddition reaction across the double or triple bond to form products inwhich the boron esters are located on adjacent carbon atoms.

The terms “halogen-like substituent” and “pseudo-halide” refer to anysubstituent which, if present on an organic compound, may react with adiboron derivative in the presence of a Group VIII metal catalyst andbase to give an organic boronic acid derivative. Preferred halogensubstituents include I and Br. Cl may also be used although Cl isgenerally less reactive to substitution by the diboron compound. Thereactivity of chloro substituted organic compounds can be increased byselection of appropriate ligands on the Group VIII metal catalyst.Examples of halogen-like substituents include triflates and mesylates,diazonium salts, phosphates and those described in Palladium Reagents &Catalysts (Innovations in Organic Synthesis by J. Tsuji, John Wiley &Sons, 1995, ISBN 0-471-95483-7).

As used herein, the term “leaving group” refers to a chemical groupwhich is capable of being displaced by a boronic acid residue. Suitableleaving groups are apparent to those skilled in the art and includehalogen and halogen-like substituents.

The temperature at which the preparation of the diboronic acid esters isconducted will depend on a number of factors including the desired rateof reaction, solubility and reactivity of the reactants in the selectedsolvent, boiling point of the solvent, etc. The temperature of thereaction will generally be in the range of −100 to 200° C. In apreferred embodiment the process is performed at a temperature between 0and 80°, more preferably between 15 and 40° C.

Chiral diboronic acid derivatives may be prepared from chiral startingmaterials or intermediates under conditions in which the chirality ispreserved or they may also be prepared via the racemate in which case aseparation step will be required. Separation of the enantiomers may beachieved conventionally using conventional chromatographic methodsincluding chiral chromatography, enzymatic resolution, or using aresolving agent. The individual chiral forms are also part of thepresent invention.

Diboron derivatives containing a chiral centre, if there is anenantiomeric excess of one isomer, are particularly useful in thepreparation of enantiomers of chiral compounds. In this regard it ispossible to react a diboron compound having one or more chiral centers,and an enantiomeric excess of one enantiomer, with an organic compoundhaving a boron reactive site to produce an organic boronic acid esterderivative in which the chirality is preserved. The chiral organicboronic acid derivative may then be reacted with another organiccompound to produce a new chiral centre, the stereochemistry of which isinduced by the stereochemistry of the chiral organic boronic acidderivative. Suitable organic compounds with which to react the chiralorganic boronic acid derivative include aldehydes and unsymmetricalketones, as reaction at the carbonyl produces a new chiral center. It isalso possible to couple sterically hindered aromatic rings via anaromatic boronic acid derivative intermediate to produce chiral biarylcompounds in which the helical sense is maintained through restrictedrotation about the bond linking the aromatic rings (also referred to asatropism).

In a particularly preferred embodiment of the invention a diboronderivative is prepared by reacting a suitable diboron reactant with achiral diol, examples include pinanediol, diisopropyl tartrate, andsugars, such as mannose or galactose and like sugars containingcis-hydroxy groups or other hydroxy groups suitably orientated to couplewith boron. The chiral diboron derivatives may then be reacted withsuitable organic compounds having boron reactive sites to produce chiralorganic boronic acid derivatives. These may be reacted in astereospecific manner with an organic compound, with the formation of anew chiral center.

It is also possible to activate the boron to boron bond by selecting anR¹ to R⁴, A, A¹, or A² substituent which is capable of furthercoordinating with one of the boron atoms. Such groups would include anelectron rich substituent or atom which is capable of feeding electrondensity onto the boron atom. Examples of electron rich atoms includeoxygen, nitrogen and sulphur.

A difficulty with using the known pinacol ester of diboronic acid toproduce organic boronic acids is that it is difficult to cleave thepinacol ester to give the corresponding organic boronic acid. Otheresters of this invention have been found to hydrolyse more readily thanthe pinacol ester. Esters containing an aromatic ring on the carbon α tothe X moiety are surprisingly easy to cleave to the correspondingboronic acid. Benzyl ester derivatives are particularly useful for thispurpose.

It is also possible to select substituents to improve the solubility ofthe diboron derivative in a particular solvent in which a subsequentreaction is to be carried out. Water solubility of the diboron compoundcan be increased by introducing polar groups, such as hydroxy groups,into the R¹ to R⁴, A, A¹ and A² substituents. Similarly it is possibleto select substituents which increase the solubility of the diboroncompound in the desired organic solvent.

Many of the boronic acid ester derivatives prepared from the noveldiboronic acid derivatives according to the present invention are alsonovel and represent a further aspect of the present invention.

These organic boronic acid derivatives may be reacted with organiccompounds having one or more boron reactive sites to produce coupledproducts, as described above. These coupling reactions are generallyconducted in the presence of a group VIII metal catalyst and a suitablebase.

The process and compounds according to the invention are also useful forthe preparation of reactive intermediates which are capable of takingpart in further reactions or rearrangements. These reactiveintermediates may be the organic boronic acid derivative or the coupledproducts. For example, organic boronic acid derivatives may take part inone or more of the palladium catalysed reactions of organoboroncompounds described by Miyaura and Suzuki in Chem. Rev. 1995, 952457-2483. Examples of other types of reactions in which the diboronderivatives of the present invention are useful are described incopending applications PCT/AU98/00245 and PCT/AU98/00476.

The invention will now be described with reference to the followingexamples which illustrate some preferred embodiments of the invention.It is to be understood that the particularity of the followingdescription is not to supersede the generality of the precedingdescription of the invention.

EXAMPLES

General Procedures

General Procedure A

Two equivalents of diol is added to a solution oftetrakis(dimethylamino)diboron in dry diethyl ether under nitrogen. Thereaction mixture is stirred magnetically and cooled in an ice-bathbefore adding a dry etheral solution of hydrogen chloride (4equivalents) over 1 h. After stirring overnight at room temperature thereaction mixture is filtered and the solid collected is extracted withhot benzene (2×) to remove the dimethylamine hydrochloride salt. Theether filtrate and the benzene extracts are taken to dryness undervacuum. The resultant products are then combined, recrystallised frombenzene/petroleum spirit (60-80° C.) and dried under high vacuum.

General Procedure B

Two equivalents of diol is added to diboronic acid in benzene and thereaction mixture heated under reflux for 24 hours using a Dean-Starkapparatus. The benzene solution is separated from the water formed,dried and taken to dryness under vacuum to give the diboronic ester. Theaddition of monoalcohols such as ethanol or methanol can be used toenhance this procedure.

General Procedure C

Two equivalents of diol is added to diboronic acid in tetrahydrofuran. Adehydrating agent such as anhydrous sodium sulphate is added and thereaction mixture stirred at room temperature overnight. The solution isthen filtered and the filtrate taken to dryness under vacuum to yieldthe diboronic ester. The addition of monoalcohols such as methanol andethanol can be used to enhance the procedure. The presence of adehydrating agent is not always necessary for satisfactory yields.

Example 10

This diboronic ester is prepared following general procedure A using(2R,3R)-(−)-2,3-butanediol. ¹H-nmr (CDCl₃, 200 MHz): δ1.22 (6H,multiplet; CHCH ₃) and 4.00 (2H, multiplet; CHCH₃).

Example 2 1,1,2,2-Tetrakis(2-methoxyethyloxy)diborane

This diboronic ester is prepared following general procedure A using2-methoxy-ethanol. ¹H-nmr (CDCl₃, 200 MHz): δ3.36 (3H, singlet; CH ₃),3.42-3.51 (2H, multiplet; BOCH ₂) and 3.62-3.71 (2H, multiplet; CH ₂O).

Example 3 Bis((1S,2S,3R,5S)-(+)-pinanediolato)diboron(B-B)

This diboronic ester is prepared following general procedure A using(1S,2S,3R,5S)-(+)-pinanediol. Yield 98% ¹H-nmr (CDCl₃, 200 MHz): δ0.77(singlet, 3H; C₃CH ₃), 1.01-1.13 (doublet, 2H; C₃CH), 1.20 (3H, singlet;C₃CH ₃), 1.87-1.91 (2H, multiplet; C₂CH ₂), 1.92-2.31 (3H, multiplet; CH₂CO and CHCO) and 4.15-4.26 (1H, multiplet; C₂(CHO).

Example 4 (4R,4′R)-Diphenyl-2,2′-bi-1,3,2-dioxaborolane

This diboronic ester is prepared following general procedure A using(R)-(−)-1-phenyl-1,2-ethanediol. Yield, 88% ¹H-nmr (CDCl₃, 200 MHz):δ3.90-4.01 (1H, triplet; CH ₂C), 4.42-4.57 (1H, triplet; CH ₂C) and7.10-7.31 (5H, multiplet; ArH). ¹³C-nmr (CDCl₃, 200 MHz): δ72.73 (1C;CH₂), 78.78 (1C; CPh) 125.71 (2C; m-C), 128.17 (1C; p-C), 128.70 (2C;o-C) and 140.65 (1C; C-O).

Example 5 4,4′-Bi-[(4-methoxyphenoxy)methyl]-2,2-′bi-1,3,2-dioxaborolane

This diboronic ester is prepared following general procedure A using3-(4-methoxyphenoxy)-1,2-propanediol. Yield, 70% ¹³C-nmr (D₆-DMSO, 200MHz): δ55.27, 66.50, 70.00, 70.74, 74.80, 114.51, 115.45, 152.30 and153.60.

Example 6 2,2′-Bi-(3aR,7aS)hexahydro-1,3,2-benzodioxaborole

This diboronic ester is prepared following general procedure A usingcis-1,2-cyclohexanediol. Yield, 65%. ¹H-mnr (CDCl₃, 200 MHz): δ1.20-2.00(multiplet, 8H; CH ₂ and 4.30 (multiplet, 2H; CH).

Example 7 Tetraisopropyl(4R,4′R,5R,5′R)-2,2′-bi-1,3,2-dioxaborolane-4,4′5,5′-tetracarboxylate

This diboronic ester is prepared following general procedure A usingdiisopropyl L-tartrate. Yield, quantitative. ¹H-nmr (CDCl₃, 200 MHz):δ1.10-1.30 (multiplet, 28H; CHCH₃ and CH ₃) and 4.30 (singlet, 4H; OCH).

Example 8(3aR,3′aR,6aS,6′aS)-Di-(tetrahydro-3aH-cyclopenta[d])-2,2′-bi-1,3,2-dioxaborolane

This diboronic ester is prepared following general procedure A usingcis-1,2-cyclopentanediol. Yield, 78% ¹H-nmr (CDCl₃, 200 MHz): δ1.40-1.61(multiplet, 4H; OCHCH₂), 1.75-2.00 (multiplet, 2H; CH₂CH₂CH ₂) and 4.80(multiplet, 2H; OCH).

Example 93R,6S,3′R,6′S)-Di-(tetrahydrofuro[3,4d])-2,2′-bi-1,3,2-dioxaborolane

This diboronic ester is prepared following general procedure A using1,4-anhydroerythiritol. Yield, 78% ¹H-nmr (CDCl₃, 200 MHz): δ3.40-3.50(multiplet, 2H; OCHH), 4.004.14 (multiplet, 2H; CHH) and 4.90(multiplet, 2H; OCH).

Example 1 4,4′-Bis(methoxymethyl)-2,2′-bi-1,3,2-dioxaborolane

This diboronic ester is prepared following general procedure A using3-methoxy-1,2-propanediol. Yield, 96% ¹H-nmr (CDCl₃, 200 MHz): δ3.23(singlet, 6H; OCH ₃), 3.30-3.40 (multiplet, 4H; CH₃OCHH), 3.80-3.95(multiplet, 2H; (multiplet, 2H; CH₃OCHH), 4.10-4.20 (triplet, 2H; CH₂OB) and 4.40-4.50 (multiplet, 2H; OCH).

Example 11 2,2′-Bi-1,3,2-dioxaborepane

This diboronic ester is prepared following general procedure A using1,4-butanediol. ¹H-nmr (D₆-DMSO, 200 MHZ): δ1.36-1.42 (multiplet, 4H;CH₂CH₂CH₂) and 3.36 (multiplet, 4H; CH₂O).

Example 125,5′-Dihydroxymethyl-5,5′-Dimethyl-2,2′-bi-1,3,2-dioxaborinane

This diboronic ester is prepared following general procedure C using1,1,1-tris(hydroxymethyl)ethane. Yield, 90% ¹H-nmr (d₆dmso; 200 MHz):δ0.79 (singlet, 6H; 2×CH ₃), 3.21-3.75 (multiplet, 12H; 6×CH ₂O) and4.76 (triplet, 2H; 2×OH). F.W.: calc. for C₁₀ H₂₀B₂O₆=257.89, found m/z259 (M+1).

Example 13 Bis(1R,2R,3S,5R-(−)-pinanediolato)diboron(B—B)

This diboronic ester is prepared following general procedure A using1R,2R,3S,5R-(−)-pinanediol. Yield, 77%. ¹H-nmr (CDCl₃, 200 MHz;): δ0.84(singlet, 6H; 2×C₃CH ₃), 1.08-1.14 (doublet, 2H; 2×C₃CH), 1.28 (singlet,6H; 2×C₃CH₃), 1.39 (singlet, 6H; 2×CH ₃CO), 1.87-1.97 (multiplet, 4H;2×C₂CH ₂), 2.04-2.37 (multiplet, 6H; 2×CH ₂CO and 2×CHCO) and 4.24-4.29(multiplet, 2H; 2×C₂CHO). F.W.: calc. for C₂₀H₃₂B₂O₄=358.09, found m/z359 (M+1).

Example 14 2,2′-Bi-4H-1,3,2-benzodioxaborinine

This diboronic ester is prepared following general procedure C using2-hydroxybenzyl alcohol. Yield, 77%. ¹H-nmr (CDCl₃, 200 MHz): δ5.12(singlet, 4H; 2×ArCH ₂), 6.91-7.26 (multiplet, 8H; 2×ArH). F.W.: calc.for C₁₄H₁₂B₂O₄=265.87, found m/z 267 (M+1).

Example 15 4,4′-Bi-(phenoxymethyl)-2,2′-1,3,2-dioxaborolane

This diboronic ester is prepared following general procedure A using3-phenoxy-1,2-propanediol. Yield, 71%. ¹H-nmr (CDCl₃, 200 MHz):δ3.96-4.41 (multiplet, 8H; 4×CH ₂O), 4.74-4.86 (multiplet, 2H; 2×OCH)and 6.86-7.34 (multiplet, 10H; 2×OArH). F.W.: calc. forC₁₈H₂₀B₂O₆=353.97, found m/z 355 (M+1).

Example 16 4,4,4′,4′,6,6′-Hexamethyl-2,2′-bi-1,3,2-dioxaborinane

This diboronic ester is prepared following general procedure A using2-methyl-2,4-pentanediol. Yield, 71%. ¹H-nmr (CDCl₃, 200 MHz):δ1.18-1.32 (multiplet, 18H; 6×CH ₃), 1.44-1.56 (multiplet, 2H; 2×HCHC),1.69-1.78 (multiplet, 2H; 2×HCHC) and 4.07-4.22 (multiplet, 2H; 2×OCH).F.W.: calc. for C₁₂H₂₄B₂O₄=253.94, found m/z 255 (M+1).

Example 17 5,5,5′,5′-Tetraethyl-2,2′-bi-1,3,2-dioxaboninane

This diboronic ester is prepared following general procedure A using2,2-diethyl-1,3-propanediol. Yield, 79%. H-nmr (CDCl₃, 200 MHz):δ0.75-0.82 (triplet, 12H; 4×CH ₃), 1.25-1.37 (quartet, 8H; 4×CH ₂CH₃)and 3.69 (singlet, 8H; 4×CH ₂O). F.W.: calc. for C₁₄H₂₈B₂O₄=282.00,found m/z 283 (M+1).

Example 18 4,4′,5,5′-Tetramethyl-2,2′-bi-1,3,2-dioxaborolane

This diboronic ester is prepared following general procedure A using2,3-butanediol. ¹H-nmr (CDCl₃, 200 MHz): δ1.10-1.28 (multiplet, 12H;4×CH ₃) and 4.42-4.52 (multiplet, 4H; 4×CH).

Example 19 4,4′-Dimethyl-2,2′-bi-1,3,2-dioxaborinane

This diboronic ester is prepared following general procedure A using1,3-butanediol. Yield, 94%. ¹H-nmr (CDCl₃, 200 MHz): δ1.21-1.25(doublet, 6H; 2×CH ₃), 1.56-1.94 (multiplet, 4H; 2×CH₂CH ₂CH) and3.81-4.14 (multiplet, 6H; 2×OCH ₂ and 2×OCH). F.W.: calc. forC₈H₁₆B₂O₄=197.83, found m/z 199 (M+1).

Example 20 5,5′-Dimethyl-2,2′-bi-1,3,2-dioxaborinane

This diboronic ester is prepared following general procedure A using2-methyl-1,3-propanediol. Yield, 96%. ¹H-nmr (CDCl₃, 200 MHz):δ0.80-0.84 (doublet, 6H; 2×CH ₃), 1.97-2.17 (multiplet, 2H; 2×CHCH₃),3.43-3.57 (triplet, 4H; 4×HCHCCH₃) and 3.87-3.95 (multiplet, 4H;4×HCHCCH3). F.W.: calc. for C₉H₁₆B₂O₄=197.83, found m/z 199 (M+1).

Example 21 Bi-(dinaphtho[2,1-d:1,2-f])-2,2′-bi-1,3,2-dioxaborepine

This diboronic ester is prepared following general procedure A using1,1′-bis-2-naphthol. ¹H-nmr (CDCl₃, 200 MHz): δ6.90-6.95 (multiplet, 2H;ArH), 7.12-147.34 (multiplet, 6H; ArH) and 7.83-7.99 (multiplet, 2H;ArH).

Example 22 6,6′-Diethyl-2,2′-bi-1,3,6,2-dioxazaborocane

This diboronic ester is prepared following a similar method to thatdescribed in general procedure C using N-ethyldiethanolamine, but thistime adding the sodium sulphate in the initial stages of the reactionand heating the mixture under reflux. ¹H-nmr (200 MHz; CDCl₃):δ1.15-1.23 (triplet, 6H; 2×CH ₃), 2.88-2.91 (multiplet, 12H; 6×CH ₂N)and 3.83-3.85 (multiplet, 8H; 4×OCH ₂).

Example 23 6,6′-Dimethyl-2,2′-bi-1,3,6,2-dioxazaborocane

This diboronic ester is prepared following general procedure B usingN-methyldiethanolamine. ¹H-nmr (200 MHz; CDCl₃): δ2.51 (triplet, 6H; CH₃), 2.79-3.35 (multiplet, 8H; 4×CH ₂N) and 3.76-3.94 (multiplet, 8H;4×CH ₂O).

Example 24 5,5,5′,5′-Tetraphenyl-2,2′-bi-1,3,2-dioxaborinane

This diboronic ester is prepared following general procedure A using2,2-diphenyl-1,3-propanediol. ¹H-nmr (CDCl₃, 200 MHz): δ4.48 (singlet,8H; CH ₂O) and 7.13-7.31 (multiplet, 20H; ArH).

Example 25 4,4,4′,4′,7,7,7′,7′-Octamethyl-2,2′-bi-1,3,2dioxaborepane

This diboronic ester is prepared following general procedure A using2,5-dimethyl-2,5-hexanediol. ¹H-nmr (CDCl₃, 200 MHz): δ1.27 (singlet,24H; CH ₃) and 1,77 (singlet, 8H; CH ₂).

Example 26 1,1,2,2-Tetrakis(neopentyloxy)diborane

This diboronic ester is prepared following general procedure A usingneopentylalcohol. ¹H-nmr (CDCl₃, 200 MHz): δ0.93 (singlet, 36H; CH ₃)and 3.62 (singlet, 8H; CH ₂). F.W.: calc. for C₂₀H₄₄B₂O₄=370.19, found(GCMS) m/z=371 (M+1).

Example 27 (4S,4′S,5S,5′S)-Tetramethyl-2,2′-bi-1,3,2-dioxaborolane

This diboronic ester is prepared following general procedure A using(2S,3S)-(+)-2,3-butanediol. Yield, quantitative. ¹H-nmr (CDCl₃, 200MHz): δ1.30 (singlet, 6H, CH ₃). 1.33 (singlet, 6H, CH ₃) and 3.99(multiplet, 4H; CH). F.W.: calc. for C₈H₁₆B₂O₄=197.83, found (GCMS)m/z=199 (M+1).

Example 28 Tetrabutyl(4R,4′R,5R,5′R)-2,2′-bi-1,3,2-dioxaborolane-4,4′,5,5′-tetracarboxylate

This diboronic ester is prepared following general procedure A usingdibutyl L-tartrate. Yield, 93%. ¹H-nmr (CDCl₃, 200 MHz): δ0.89-0.98(multiplet, 12H; CH ₃), 1.27-1.47 (multiplet, 8H; CH ₂CH₃), 1.58-1.72(multiplet, 8H; CH₂CH ₂CH₂), 4.15-4.25 (multiplet, 8H; CH ₂O) and 4.92(singlet, 4H; CHCO₂). The desired compound was detected by GCMS.

Example 29(4R,4′R,5R,5′R)-N⁴,N⁴,N^(4′),N^(4′),N⁵,N⁵,N^(5′),N^(5′)-Octamethyl-2,2′-bi-1,3,2-dioxaborolane-4,4′,5,5′-tetracarboxamide

This diboronic ester is prepared following general procedure A usingN,N,N′,N′-tetramethyl L-tartaramide. Yield, 74%. ¹H-nmr (CDCl₃, 200MHz): δ2.90 (singlet, 12H; NCH ₃), 3.14 (singlet, 12H; NCH ₃) and 5.54(singlet, 4H; CHC═O).

Example 30 4,4,4′,4′-Tetramethyl-2,2′-bi-1,3,2-dioxaborinane

Synthesis of

The diol 2-methyl-2,4-dihydroxybutane (1.04 g, 1 mmol) was reacted withdiboronic acid (0.45 g, 0.5 mmol) in 25 ml dry THF at room temp.(procedure C without dehydrating agent). The diboronic acid rapidlydissolved to give a colourless, clear solution. The gc on a smallaliquot of the reaction solution, diluted with ethyl acetate, showedonly two peaks of area ratio 2:98. The weak peak corresponded to theretention time of the diol. On removing the solvent from the reactionsolution under reduced pressure the product ester was obtained as awhite solid. ¹H nmr (CDCl₃) δ1.30 (s, 12H), 1.78 (t, J=5.8 Hz, 4H), 3.98(t, J=5.8 Hz, 4H).

Example 31 4,4,4′,4′,6,6,6′,6′-Octamethyl-2,2′-bi-1,3,2-dioxaborinane

Synthesis of

The diol 2,4-dimethyl-2,4-dihydroxypentane (1.32 g, 1 mmol) was reactedwith diboronic acid (0.45 g, 0.5 mmol) in 25 ml dry THF at room temp.(procedure C without dehydrating agent). The diboronic acid dissolved togive a colourless, clear solution. The gc on a small aliquot of thereaction solution, diluted with ethyl acetate, showed only two peaks ofarea ratio 4:95. The weak peak corresponded to the retention time of thediol. On removing the solvent from the reaction solution under reducedpressure the product ester was obtained as a white solid. ¹H nmr(D₆-DMSO) δ1.25 (s, 24H), 1.77 (s, 4H).

Example 32 3,3′-Bi-1,5-dihydro-2,4,3-benzodioxaborepine

Synthesis of

The diol 1,2-benzenedimethanol (1.38 g, 1 mmol) was reacted withdiboronic acid (0.45 g, 0.5 mmol) in 25 ml dry THF at room temp.(procedure C without dehydrating agent). After most of the diboronicacid had dissolved, the reaction was warmed to 50-55° C. for severalhours and then filtered to give a clear, colourless solution. Thesolvent was removed from the compound under reduced pressure and awhite, soft compound was obtained. ¹H nmr (CDCl₃) gave three broad peaksat δ4.74, 4.89, 5.01 and a sharp singlet at 5.10 (total 8H), and twomultiplets at 7.22 and 7.28 (total 8H). The broad peaks sharpened oncooling the CDCl₃ solution and are possibly due to isomers of thedesired compound.

The formation of the ester, at room temp., is considerably faster inethanol than in THF, all the diboronic acid (0.45 g, 0.5 mmol) reactingwith the diol 1,2-benzenedimethanol (1.38 g, 1 mmol) within severalminutes following solvent addition (25 ml) to give a clear, colourlesssolution. This was stirred at room temperature before removal of thesolvent under reduced pressure. A white, hard solid was obtained, freefrom ethanol (¹H nmr) after pumping on the material for several hours at10⁻⁷ to 10⁻¹ mmHg and temperature around 40° C. ¹H nmr (CDCl₃) δ4.73(s),5.09(s) (intensity ratio 1:4.3, total 8H,), and 7.23 and 7.32 (total8H). The peaks at δ4.73 and 7.31 are weak and may be due to an isomer ofthe product in which the ligands bridge the two boron atoms.

Example 33 4,4,4′,4′,5,5′-Hexamethyl-2,2′-bi-1,3,2-dioxaborolane

This diboronic ester is prepared following general procedure A using2-methyl-2,3-butanediol. ¹H-nmr (CDCl₃, 200 MHz): δ0.75-1.18 (multiplet,CH ₃ and CH). F.W.: calc. for C₁₀H₂₀B₂O₄=225.89, found (GCMS) m/z=226(M+1).

Example 34 4,4′,4′-Tetramethyl-2,2′-bi-1,3,2-dioxaborolane

This diboronic ester is prepared following general procedure A using2-methylpropane-1,2diol. ¹H-nmr (CDCl₃, 200 MHz): δ1.22 (singlet, 12H;CH ₃) and 3.73 (singlet, 4H; CH ₂). F.W.: calc. for C₈H₁₆B₂O₄=197.83,found (GCMS) m/z=198 (M+1).

TABLE 1 IUPAC Nomenclature: Compound Compound Name Example 1(4R,4′R,5R,5′R)-Tetramethyl-2,2′-bi-1,3,2-dioxaborolane. Example 21,1,2,2-Tetrakis(2-methoxyethyloxy)diborane. Example 3Bis((1S,2S,3R,5S)-(+)-pinanediolato)diboron(B—B). Example 4(4R,4′R)-Diphenyl-2,2′-bi-1,3,2-dioxaborolane. Example 54,4′-Bi-[(4-methoxyphenoxy)methyl]-2,2′-bi-1,3,2- dioxaborolane. Example6 2,2′-Bi-(3aR,7aS)hexahydro-1,3,2-benzodioxaborole. Example 7Tetraisopropyl (4R,4′R,5R,5′R)-2,2′-bi-1,3,2-dioxaborolane-4,4′5,5′-tetracarboxylate. Example 8(3aR,3′aR,6aS,6′aS)-Di-(tetrahydro-3aH-cyclopenta[d])-2,2′-bi-1,3,2-dioxaborolane. Example 9(3R,6S,3′R,6′S)-Di-(tetrahydrofuro[3,4-d])-2,2′-bi-1,3,2- dioxaborolane.Example 10 4,4′-Bis(methoxymethyl)-2,2′-bi-1,3,2-dioxaborolane. Example11 2,2′-Bi-1,3,2-dioxaborepane. Example 125,5′-Dihydroxymethyl-5,5′-Dimethyl-2,2′-bi-1,3,2- dioxaborinane. Example13 Bis(1R,2R,3S,5R-(-)-pinanediolato)diboron(B—B). Example 142,2′-Bi-4H-1,3,2-benzodioxaborinine. Example 154,4′-Bi-(phenoxymethyl)-2,2′-1,3,2-dioxaborolane. Example 164,4,4′,4′,6,6′-Hexamethyl-2,2′-bi-1,3,2-dioxaborinane. Example 175,5,5′,5′-Tetraethyl-2,2′-bi-1,3,2-dioxaborinane. Example 184,4′,5,5′-Tetramethyl-2,2′-bi-1,3,2-dioxaborolane. Example 194,4′-Dimethyl-2,2′-bi-1,3,2-dioxaborinane. Example 205,5′-Dimethyl-2,2′-bi-1,3,2-dioxaborinane. Example 21Bi-(dinaphtho[2,1-d: 1,2-f])-2,2′-bi-1,3,2-dioxaborepine. Example 226,6′-Diethyl-2,2′-bi-1,3,6,2-dioxazaborocane. Example 236,6′-Dimethyl-2,2′-bi-1,3,6,2-dioxazaborocane. Example 245,5,5′,5′-Tetraphenyl-2,2′-bi-1,3,2-dioxaborinane. Example 254,4,4′,4′,7,7,7′,7′-Octamethyl-2,2′-bi-1,3,2dioxaborepane. Example 261,1,2,2-Tetrakis(neopentyloxy)diborane. Example 27(4S,4′S,5S,5′S)-Tetramethyl-2,2′-bi-1,3,2-dioxaborolane. Example 28Tetrabutyl (4R,4′R,5R,5′R)-2,2′-bi-1,3,2-dioxaborolane-4,4′,5,5′-tetracarboxylate. Example 29(4R,4′R,5R,5′R)-N⁴,N⁴,N^(4′),N^(4′),N⁵,N⁵,N^(5′),N^(5′)-Octamethyl-2,2′-bi-1,3,2-dioxaborolane-4,4′,5,5′-tetracarboxamide. Example 304,4,4′,4′-Tetramethyl-2,2′-bi-1,3,2-dioxaborinane. Example 314,4,4′,4′,6,6,6′,6′-Octamethyl-2,2′-bi-1,3,2-dioxaborinane. Example 323,3′-Bi-1,5-dihydro-2,4,3-benzodioxaborepine. Example 334,4,4′,4′,5,5′-Hexamethyl-2,2′-bi-1,3,2-dioxaborolane. Example 344,4,4′,4′-Tetramethyl-2,2′-bi-1,3,2-dioxaborolane.

Throughout this specification and the claims which follow, unless thecontext requires otherwise, the word “comprise”, or variations such as“comprises” or “comprising”, will be understood to imply the inclusionof a stated integer or group of integers but not the exclusion of anyother integer or group of integers.

Those skilled in the art will appreciate that the invention describedherein is susceptible to variations and modifications other than thosespecifically described. It is to be understood that the inventionincludes all such variations and modifications. The invention alsoincludes all of the steps, features, compositions and compounds referredto or indicated in the specification, individually or collectively, andany and all combinations of any two or more of said steps or features.

What is claimed is:
 1. A process for the preparation of a diboronic acidester comprising contacting tetrahydroxydiboron with a suitablemonoalcohol, diol or polyol in the presence of an appropriate solvent ormixture of solvents and at a temperature between room temperature andthe boiling point of the solvent at ambient pressure such that thetetrahydroxydiboron reacts with the monoalcohol, diol or polyol to formthe diboronic acid ester.
 2. A process according to claim 1 wherein thetetrahydroxydiboron is reacted with a diol or polyol in a solventcomprising a monoalcohol.
 3. A process according to claim 2 wherein themonoalcohol is a lower alkanol.
 4. A process according to claim 3wherein at least four equivalents of monoalcohol are used and theproduct formed between the tetrahydroxydiboron and the monoalcoholreacts with the diol or polyol by transesterification to thereby formthe diboronic acid ester.
 5. A process according to claim 3 wherein thelower alkanol is methanol or ethanol.
 6. A process according to claim 1performed in the absence of an acid catalyst.